A Study of the C3 Inhibitor AMY-101 in Patients With ARDS Due to COVID-19 (SAVE)
Study Details
Study Description
Brief Summary
The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection.
We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AMY-101
|
Drug: AMY-101
C3 complement inhibitor
|
| Placebo Comparator: Placebo
|
Other: WFI 5% glucose
Placebo
|
Outcome Measures
Primary Outcome Measures
- The proportion of patients who are alive, without evidence of ARDS (i.e. PaO2/FIO2 >300 mm Hg), who do not require any oxygen support (in room air). [21 days]
- The proportion of patients assigned to each category, of a six-category ordinal scale. [21 days]
The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.
Secondary Outcome Measures
- The proportion of patients assigned to each category, of a six-category ordinal scale. [On days 7, 14, and 44]
The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.
- Proportion of patients surviving [Through to day 44]
- Proportion of respiratory failure-free survival [Day 44]
With respiratory failure defined as any of the following: Worsening of severe gas transfer deficit, accounting for a shift in ARDS disease category (PaO2/FiO2 ≤200 for patients with PaO2/FiO2 >200 at baseline; PaO2/FiO2 ≤100 for patients with PaO2/FiO2 >100 at baseline), Persistent respiratory distress while receiving oxygen (persistent marked dyspnea,use of accessory respiratory muscles, paradoxical respiratory movements), Transfer to the intensive care unit for intubation, Death.
- Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air) [Through day 44]
- Cumulative incidence of freedom from oxygen requirement [Through day 44]
- Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS [Within 14 days after inclusion in the study]
- Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS [Within 14 days after inclusion in the study]
- Proportion of patients developing thrombotic microangiopathies [Through day 44]
- Changes in PaO2 and PaO2/FIO2 [Through day 44]
- Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS) [Through day 44]
- Changes in maximal and minimal cardiovascular parameters: Respiratory rate [Through day 44]
- Changes in maximal and minimal cardiovascular parameters: Heart Rate [Through day 44]
- Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH) [On days 0, 1, 2, 4, 7, 10, 14, 21 and 44]
- Length of stay in ICU [Through day 44]
- Cumulative incidence of discharge from hospital [Through day 44]
- Number of adverse events [Through day 44]
- Changes in levels of anti-drug antibodies [On day 0 , 14 and 44]
- Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9 [On days 0, 1, 2, 4, 7, 10, 14, 21 and 44]
- Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12 [On days 0, 1, 2, 4, 7, 10, 14, 21 and 44]
- Changes in levels of Club Cell protein CC16 (biomarker of lung damage ) [On days 0, 1, 2, 4, 7, 10, 14, 21 and 44]
- Changes in levels of AMY-101 plasma level [On days 1, 2, 4, 7, 10, 14, 15, 21]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Diagnosed with Acute Respiratory Distress Syndrome due to SARS-CoV-2 infection (severe
Covid-19), according to the following criteria:
-
Demonstration of SARS-CoV-2 RNAemia in nasopharyngeal swap or bronchio-alveolar lavage (BAL)
-
A ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2), PaO2/FIO2, ≤300 mmHg
-
Mild ARDS (PaO2/FIO2, ≤300 and >200 mm Hg);
-
Moderate ARDS (PaO2/FIO2, ≤200 and >100 mm Hg);
-
Severe ARDS (PaO2/FIO2, ≤100 mm Hg);
- Pulmonary infiltrates suggestive of SARS-COV-2-related ARDS: e.g., bilateral infiltrates at chest X-ray or B-lines at lung US scan.
- Dated and signed informed consent from patient or legal represantative.
Exclusion Criteria:
-
Intubated patients
-
Demonstrated or suspected uncontrolled systemic severe infection, such as sepsis (e.g.: positive blood culture, or procalcitonin ≥0.25 µg/L)
-
Demonstrated local extrapulmonary abscess
-
ARDS due to cardiac failure or fluid overload
-
Concomitant treatment with immunomodulatory /immunosuppressive drugs , which have potential activity against the disease
-
Multi Organ Failure (MOF)
-
Severe renal failure (CKD, by defition glomerular filtration rate <30 ml/min)
-
Neisseria meningitidis infection that is not resolved
-
Current treatment with a complement inhibitor
-
Intravenous immunoglobulin (IVIg) within 3 weeks prior to Screening
-
Participation in another interventional treatment study within 30 days before initiation of the study treatment (Day 1 in this study) or within 5 half-lives of that investigational product, whichever is greater.
-
Chemotherapy for less than 3months
-
Pregnancy
-
Age <18.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amyndas Pharmaceuticals S.A.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Mastaglio S, Ruggeri A, Risitano AM, Angelillo P, Yancopoulou D, Mastellos DC, Huber-Lang M, Piemontese S, Assanelli A, Garlanda C, Lambris JD, Ciceri F. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020 Jun;215:108450. doi: 10.1016/j.clim.2020.108450. Epub 2020 Apr 29.
- Risitano AM, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD. Complement as a target in COVID-19? Nat Rev Immunol. 2020 Jun;20(6):343-344. doi: 10.1038/s41577-020-0320-7. Epub 2020 Apr 23. Erratum in: Nat Rev Immunol. 2020 Jul;20(7):448.
- AMY-101_SAVE